Tommaso Zoerle

Severe traumatic brain injury: targeted management in the intensive care unit

Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical-surgical approach. Treatment aims to prevent additional brain damage and to optimise conditions for brain recovery. TBI is typically considered and treated as one pathological entity, although in fact it is a syndrome comprising a range of lesions that can require different therapies and physiological goals. Owing to advances in monitoring and imaging, there is now the potential to identify specific mechanisms of brain damage and to better target treatment to individuals or subsets of patients. Targeted treatment is especially relevant for elderly people-who now represent an increasing proportion of patients with TBI-as preinjury comorbidities and their therapies demand tailored management strategies. Progress in monitoring and in understanding pathophysiological mechanisms of TBI could change current management in the intensive care unit, enabling targeted interventions that could ultimately improve outcomes.

Rethinking Neuroprotection in Severe Traumatic Brain Injury: Toward Bedside Neuroprotection

Neuroprotection after traumatic brain injury (TBI) is an important goal pursued strenuously in the last 30 years. The acute cerebral injury triggers a cascade of biochemical events that may worsen the integrity, function, and connectivity of the brain cells and decrease the chance of functional recovery. A number of molecules acting against this deleterious cascade have been tested in the experimental setting, often with preliminary encouraging results. Unfortunately, clinical trials using those candidate neuroprotectants molecules have consistently produced disappointing results, highlighting the necessity of improving the research standards. Despite repeated failures in pharmacological neuroprotection, TBI treatment in neurointensive care units has achieved outcome improvement. It is likely that intensive treatment has contributed to this progress offering a different kind of neuroprotection, based on a careful prevention and limitations of intracranial and systemic threats. The natural course of acute brain damage, in fact, is often complicated by additional adverse events, like the development of intracranial hypertension, brain hypoxia, or hypoperfusion. All these events may lead to additional brain damage and worsen outcome. An approach designed for early identification and prompt correction of insults may, therefore, limit brain damage and improve results.

Virtual Reality for Traumatic Brain Injury

In this perspective, we discuss the potential of virtual reality (VR) in the assessment and rehabilitation of traumatic brain injury, a silent epidemic of extremely high burden and no pharmacological therapy available. VR, endorsed by the mobile and gaming industries, is now available in more usable and cheaper tools allowing its therapeutic engagement both at the bedside and during the daily life at chronic stages after injury with terrific potential for a longitudinal disease modifying effect.

Intracranial pressure management in patients with traumatic brain injury: an update.

Purpose of review Intracranial pressure (ICP) monitoring and treatment is central in the management of traumatic brain injury. Despite 4 decades of clinical use, several aspects remain controversial, including the indications for ICP and treatment options. Recent findings Two major trials tested surgical decompression and mild hypothermia as treatments for high ICP. Both were rigorous, randomized, multicenter studies, with different designs. Decompression was tested for ICP refractory to conventional treatment, whereas hypothermia was offered as an alternative to conventional medical therapy. Decompression reduced mortality, but at the expense of more disability. The hypothermia trial was stopped because of a worse outcome in the treated arm. Indications for ICP monitoring have been reviewed and new international guidelines issued. New contributions published in 2016 have dealt with computerized analysis for predicting ICP crises; noninvasive or innovative methods for measuring ICP; reassessment of standard therapeutic interventions, such as hypertonic solutions and the level of intensity of ICP therapy. Summary Aggressive strategies for ICP control, like surgical decompression or hypothermia, carefully tested, have controversial effects on outcome. Several articles have made worthwhile contributions to important clinical issues, but with no real breakthroughs.

Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults

Background: Near‐infrared spectroscopy, a non‐invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra‐cranial contamination. Ultrasound‐tagged near‐infrared spectroscopy (UT‐NIRS) has been proposed as an improvement over previous methods. We investigated UT‐NIRS in healthy volunteers and in brain‐dead patients. Methods: We studied 20 healthy volunteers and 20 brain‐dead patients with two UT‐NIRS devices, CerOx™ and c‐FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11–300) min. In 11 cases, we obtained further demonstration of absent CBF. Results: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain‐dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter‐quartile range) CFI was 41 (36–47), significantly higher than in volunteers (33; 27–36). Conclusions: In brain‐dead patients, where CBF is absent, the UT‐NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra‐cranial structures from a genuine appraisal of cerebral perfusion. For non‐invasive assessment of CBF‐related parameters, the near‐infrared spectroscopy still needs substantial improvement.

Animal Models of SAH and Their Translation to Clinical SAH

Animal models of stroke may be useful for elucidating mechanisms of disease, but they have arguably not been particularly successful at predicting what treatments will be successful for ischemic stroke in humans. Animal models of subarachnoid hemorrhage also have been developed in rodents, dogs, and nonhuman primates. These models mimic angiographic vasospasm and some aspects of subarachnoid hemorrhage such as the transient global ischemia that sometimes occurs at the time of rupture of an aneurysm. Since the detailed acute and delayed pathologic effects of subarachnoid hemorrhage on human brain are not well delineated, how the animal models replicate this is unknown. Nevertheless, meta-analysis of the literature suggests that clinical trials of drugs for angiographic vasospasm in humans have been effective, and that some animal models accurately reflect what the effects of drugs are in humans. Analysis of animal models and comparison of drug effects on angiographic vasospasm in humans and animals suggest injection of autologous blood into the basal cisterns; assessment of vasospasm more than 3 days after the injection and intrathecal delivery of drugs may be better ways to study drugs in animals, in terms of translation to success in humans.

Fluid Management in Acute Brain Injury

Purpose of the ReviewThe aims of fluid management in acute brain injury are to preserve or restore physiology and guarantee appropriate tissue perfusion, avoiding potential iatrogenic effects. We reviewed the literature, focusing on the clinical implications of the selected papers. Our purposes were to summarize the principles regulating the distribution of water between the intracellular, interstitial, and plasma compartments in the normal and the injured brain, and to clarify how these principles could guide fluid administration, with special reference to intracranial pressure control.Recent FindingsAlthough a considerable amount of research has been published on this topic and in general on fluid management in acute illness, the quality of the evidence tends to vary. Intravascular volume management should aim for euvolemia. There is evidence of harm with aggressive administration of fluid aimed at achieving hypervolemia in cases of subarachnoid hemorrhage. Isotonic crystalloids should be the preferred agents for volume replacement, while colloids, glucose-containing hypotonic solutions, and other hypotonic solutions or albumin should be avoided. Osmotherapy seems to be effective in intracranial hypertension management; however, there is no clear evidence regarding the superiority of hypertonic saline over mannitol.SummaryFluid therapy plays an important role in the management of acute brain injury patients. However, fluids are a double-edged weapon because of the potential risk of hyper-hydration, hypo- or hyper-osmolar conditions, which may unfavorably affect the clinical course and the outcome.